The goals of this project renewal are threefold: (1) to continue studies of the rate and mechanism of clearance of radiolabeled inactivated influenza virus from the lung, (2) to determine the role of alveolar macrophages in the regulation of the ensuing immune responses to virus, and (3) to determine the mechanism by which immune cells accumulate in the lung. Clearance will be studied by inoculating radioiodinated virus into the lund and following its clearance by gamma counting as well as by utilizing autoradiographic techniques at both the light and electron microscope level. Both in vitro and in vivo studies will focus on the role of the alveolar macrophage in the uptake and degradation of virus. The role of alveolar macrophages in the induction of T lymphocyte responses will be studied in vitro by culturing nonimmune populations of pure T lymphocytes with alveolar macrophages and antigen and in vivo by inoculating nonimmune inbred guinea pigs with antigen-bearing alveolar macrophages and testing for a subsequent immune response. The mechansim of accumulation of specific B and T cells within the lung will be studied by adoptively transferring immune cells from various lymphoid organs and quantitating their accumulation in the lung both in the presence and in the absence of antigen. The long term goal of these studies is to gain a better understanding of the mechanism by which viral antigens in the lung induce local and systemic immune responses. Insight into these mechanisms should provide the basis for developing effective treatment and immunization protocols for influenza and other viral respiratory diseases.